Posted by Adam on August 12, 2001, at 18:46:03
In reply to Re: Grapefruit juice inhibition » Adam, posted by medlib on August 9, 2001, at 21:55:29
You are right about everything above.
There is a potentially big hole in my theory: A recent report in a British journal, where they used a very specific inhibitor of 3A4 in human subjects (as opposed to using liver microsomes in vitro, etc.), showed NO change in selegiline metabolism. In vitro work can be highly predictive, and has pointed directly to 3A4, but the proof is in the in vivo confirmation, and that would appear to be negative for 3A4. More work should be done to support this, but I now consider the odds at best even that 3A4 is the enzyme to target.
This is not to say grapefruit juice could not have an effect, for the reasons you mentioned above, and for the reasons of inhibition of exclusion due to interferance with P-glycoprotein, and others yet undiscovered. My hope that my doctor will be as intrigued as yours kindly was is about zero.
I guess I should start looking for someone interested in new ideas, and in colaborating with me. I wish I could find a doctor like that. I don't mind so much being wrong. I get so discouraged when my logic is simply dismissed with benevolent condescention. These ideas, though perhaps not completely informed with the relevant facts, are NOT completely hare-brained. The more I read the more I have discovered that some doctors actually exploit metabolic inhibition of one form or another for therapeutic purposes. It requires a skilled and creative pharmacologist, but it can be done.
BTW, I carefully monitored the b.p. readings from the first indicator there was a problem. I had two abnormal readings in the doctor's office spaced four days apart. I was abnormal for about a week. I stopped the diphenhydramine four or five days ago, and, despite a resultant bout of severe insomnia (exacerbated by late-night highs of around 160+ systolic), my b.p. has slowly improved, and is now about normal.
So go figure. I'm getting tested for pheochromocytoma. We'll see how hit goes.
> Hi Adam--
>
> I saw my pdoc this afternoon for my monthly 15 minutes. During a discussion of rx augmentation in order to diminish intolerable side effects of an otherwise helpful drug, I mentioned your notion of grapefruit juice to inhibit intestinal CYP3A4 metabolism of selegiline (sans names or any other details, of course). He pronounced the idea "intriguing" and "very creative" and asked that I let him know the results if it was implemented. Just thought I'd let you know you've interested one pdoc, at least.
>
> One other point: In your research, did you notice that grapefruit juice inhibits CYP1A2 as well as 3A4? I realize that 1A2 is not mostly in the gut as 3A4 is, but 1A2 inhibition is potentially relevant because acetaminophen and caffeine are among this isoenzyme's substrates. So, lots of grapefruit juice may prolong or enhance the effects of these common substances.
>
> And a question: How do your latest vital signs compare with earlier? Of course, l reading doesn't tell you jack, and it's probably too early to expect much change, but I'd think that peak and trough VSs over several days would show some downward trend, if you're on the right track.
>
> Well wishes and fingers crossed---medlib
poster:Adam
thread:74266
URL: http://www.dr-bob.org/babble/20010809/msgs/74821.html